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Journal of Nuclear Medicine Vol. 47 No. 6 974-980
© 2006 by Society of Nuclear Medicine


Basic Science Investigation

Noninvasive Measurement of Cardiovascular Function in Mice with High-Temporal-Resolution Small-Animal PET

Michael C. Kreissl1, Hsiao-Ming Wu1, David B. Stout2, Waldemar Ladno2, Thomas H. Schindler1, Xiaoli Zhang1, John O. Prior1, Mayumi L. Prins3, Arion F. Chatziioannou2, Sung-Cheng Huang1 and Heinrich R. Schelbert1

1 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California; 2 Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California; and 3 Division of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California

Correspondence: For correspondence or reprints contact: Heinrich R. Schelbert, MD, PhD, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Box 956948, B2-085J CHS, 10833 Le Conte Ave., Los Angeles, CA 90095-6948. E-mail: hschelbert{at}mednet.ucla.edu Guest Editor: Frank Bengel

The aim of this study was to explore the feasibility of determining parameters of cardiovascular function in mice noninvasively by high-temporal-resolution imaging with a dedicated small-animal PET system. Methods: Twenty-five anesthetized mice (28.8 ± 4.6 g) were injected via an intravenous catheter with a 30-µL bolus of 18F-FDG (8–44 MBq). The first 9 s of data were reconstructed into 30 frames of 0.3 s using filtered backprojection. The time–activity curve derived from a left ventricle volume of interest was corrected for tracer recirculation and partial volume. Cardiac output was calculated by the Stewart-Hamilton method, in which cardiac output is total injected activity divided by the area under the left ventricle time–activity curve. Cardiac output divided by body weight was defined as cardiac index; cardiac output divided by heart rate yielded the stroke volume. In 5 mice, measurements were repeated 2–4 times to assess reproducibility. In 4 mice, the hemodynamic response to dobutamine was examined by measuring heart rate, cardiac output, and stroke volume. Results: The cardiac output averaged 20.4 ± 3.4 mL/min; in the repeated measurements, the parameter displayed a mean percentage SD per mouse of 10% ± 6%. The cardiac index averaged 0.73 ± 0.19 mL/min/g and the stroke volume 45.0 ± 6.9 µL, and both correlated with heart rate (r = 0.53, P = 0.007, and r = 0.49, P = 0.01, respectively). During dobutamine stress, heart rate increased from 423 ± 50 to 603 ± 30 beats/min (P = 0.002) and cardiac output increased from 18.5 ± 1.9 to 32.0 ± 4.2 mL/min (P = 0.008). Conclusion: Parameters of cardiovascular function can be measured in mice noninvasively by radionuclide angiography using high-temporal-resolution small-animal PET. Measured values of cardiac output and stroke volume are reproducible and comparable to those obtained with MRI. The approach permits the monitoring of changes in cardiovascular function in response to pharmacologic intervention.

Key Words: cardiac output • microPET • cardiovascular • mouse • dynamic




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